Abstract
How mitochondrial glutaminolysis contributes to redox homeostasis in cancer cells remains unclear. Here we report that the mitochondrial enzyme glutamate dehydrogenase 1 (GDH1) is commonly upregulated in human cancers. GDH1 is important for redox homeostasis in cancer cells by controlling the intracellular levels of its product alpha-ketoglutarate and subsequent metabolite fumarate. Mechanistically, fumarate binds to and activates a reactive oxygen species scavenging enzyme glutathione peroxidase 1. Targeting GDH1 by shRNA or a small molecule inhibitor R162 resulted in imbalanced redox homeostasis, leading to attenuated cancer cell proliferation and tumor growth.
Original language | English (US) |
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Pages (from-to) | 257-270 |
Number of pages | 14 |
Journal | Cancer Cell |
Volume | 27 |
Issue number | 2 |
DOIs | |
State | Published - Feb 9 2015 |
ASJC Scopus subject areas
- Oncology
- Cancer Research